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Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy., (© 2024. The Author(s).)

Background: Disrupted sleep and rest-activity pattern are common clinical features in depressed individuals. This meta-analysis compared sleep and circadian rest-activity rhythms in people with major depressive disorder (MDD) or depressive symptoms and healthy controls., Methods: Eligible studies were identified in five databases up to December 2023. The search yielded 53 studies with a total of 11,115 participants, including 4000 depressed participants and 7115 healthy controls., Results: Pooled meta-analyses demonstrated that depressed individuals have significantly longer sleep latency (SMD = 0.23, 95 % CI: 0.12 to 0.33) and wake time after sleep onset (SMD = 0.37, 95 % CI: 0.22 to 0.52), lower sleep efficiency (SMD = -0.41, 95 % CI: -0.56 to -0.25), more nocturnal awakenings (SMD = 0.58, 95 % CI: 0.29 to 0.88), lower MESOR (SMD = -0.54, 95 % CI: -0.81 to -0.28), amplitude (SMD = -0.33, 95 % CI: -0.57 to -0.09), and interdaily stability (SMD = -0.17, 95 % CI: -0.28 to -0.05), less daytime (SMD = -0.79, 95 % CI: -1.08 to -0.49) and total activities (SMD = -0.89, 95 % CI: -1.28 to -0.50) when compared with healthy controls., Limitations: Most of the included studies reported separate sleep and activity parameters instead of 24-hour rest-activity rhythms. The variabilities among actigraphy devices and the types of participants recruited also impede precise comparisons., Conclusions: The findings emerging from this study offered a better understanding of sleep and rest-activity rhythm in individuals with MDD or depressive symptoms. Future studies could advocate for deriving objective, distinctive 24-hour rest-activity profiles contributing to the risk of depression., Prospero Registration Number: CRD42021259780., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mechanistically targeted behavioral interventions are a much-needed strategy for improving outcomes in depression, especially for vulnerable populations with comorbidities such as obesity. Such interventions may change behavior and outcome by changing underlying neural circuit function. However, it is unknown how these circuit-level modifications unfold over intervention and how individual differences in early circuit-level modifications may explain the heterogeneity of treatment effects. We addressed this need within a clinical trial of problem-solving therapy for participants with depression symptoms and comorbid obesity, focusing on the cognitive control circuit as a putative neural mechanism of action. Functional magnetic resonance imaging was applied to measure the cognitive control circuit activity at five time points over 24 months. Compared with participants who received usual care, those receiving problem-solving therapy showed that attenuations in cognitive control circuit activity were associated with enhanced problem-solving ability, which suggests that this circuit plays a key role in the mechanisms of problem-solving therapy. Attenuations in circuit activity were also associated with improved depression symptoms. Changes in cognitive control circuit activity at 2 months better predicted changes in problem-solving ability and depression symptoms at 6, 12, and 24 months, with predictive improvements ranging from 17.8 to 104.0%, exceeding baseline demographic and symptom characteristics. Our findings suggest that targeting the circuit mechanism of action could enhance the prediction of treatment outcomes, warranting future model refinement and improvement to pave the way for its clinical application.

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset 1 . Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals 2-4 , but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time., (© 2024. The Author(s).)

Objectives: To investigate the association between pain and sleep quality, anxiety, depression, body perception, and biological rhythm in chronic scrotal pain (CSP)., Material and Methods: This cross-sectional study of 140 CSP patients was conducted between January and October 2023. The patients were separated into groups according to the Visual Analogue Scale (VAS) score as group 1 (score<3, n=27), group 2 (score: 3-6, n=84), and group 3 (score>6, n=29). In addition to demographic data, the points were recorded from the Body Image Scale (BIS), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Hospital Anxiety and Depression Scale (HADS), and the Pittsburgh Sleep Quality Index (PSQI)., Results: The median (IQR) age of patients was 33 (20) years and the median (IQR) duration of pain was 5 (9) months. Group 3 patients had more anxiety (24.1% vs. group 1: 22.2%; group 2: 8.3%; P=0.03) and depression (55.2% vs. group 1: 40.7%; group 2: 29.8%; P=0.04) symptoms. No statistical differences were determined between the groups according to the BIS (P=0.54). The median (IQR) total BRIAN score was higher in group 3 than group 1 [37 (11) vs. 33 (13), P=0.03]. Higher rates of poor sleep quality were determined in group 3 patients according to the PSQI (75.9% vs. group 1: 48.1%; group 2: 51.2%; P=0.04). The VAS score was found to be positively associated with pain duration, total BRIAN score and PSQI score (r=0.31, P<0.001; r=0.17, P=0.04; r=0.23, P=0.006, respectively). The PSQI score was found to be an independent predictor for a higher VAS score (HR: 1.14, P=0.01)., Conclusion: The results of this study suggest that poor sleep quality may influence the perceived intensity of pain., Level of Evidence: II., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Maternal separation can have long-lasting effects on an individual's susceptibility to stress later in life. Maternal separation during the postnatal period is a commonly used paradigm in rodents to investigate the effects of early life stress on neurobehavioural changes and stress responsiveness. However, maternal separation during stress hyporesponsive and responsive periods of postnatal development may differ in its effects on stress resilience. Therefore, we hypothesised that late maternal separation (LMS) from postnatal day 10 to 21 in mice may have different effect on resilience than early maternal separation during the first week of postnatal life. Our results suggested that male LMS mice are more resilient to chronic variable stress (CVS)-induced anxiety and depressive-like behaviour as confirmed by the open field, light-dark field, elevated plus maze, sucrose preference and tail suspension tests. In contrast, female LMS mice were equally resilient as non-LMS female mice. We found increased expression of NPY , NPY1R , NPY2R, NPFFR1, and NPFFR2 in the hypothalamus of male LMS mice whereas the opposite effect was observed in the hippocampus. LMS in male and female mice did not affect circulating corticosterone levels in response to psychological or physiological stressors. Thus, LMS renders male mice resilient to CVS-induced neurobehavioural disorders in adulthood.

Objective: As a prodromal stage to major depressive disorder (MDD), subthreshold depression (StD) has a higher prevalence in the population, resulting in a greater healthcare burden. StD individuals' current negative emotion could be moderated by attentional deployment. However, it remains unclear whether attentional deployment training can mitigate subsequent negative emotion in StD individuals., Methods: Based on 160 participants, we combined decision task (Experiment 1, N = 69), eye-tracking (Experiment 2, N = 40), and EEG (Experiment 3, N = 51) techniques to investigate how one-week attentional deployment (gain-focus, GF) training modulated the emotional processing of negative stimulus and its underlying neural correlates in StD individuals., Results: After one-week GF training, StD individuals significantly reduced the first fixation time and total fixation time on the negative part (missed opportunities) of decision outcome and showed a decrease in emotional sensitivity to missed opportunities. An increase in N1 and decrease in P3 and LPP (late positive potentials) amplitudes, as well as a decrease in alpha oscillation, were observed when StD individuals faced missed opportunities after training. Additionally, the extent of reduction in StD individuals' emotional sensitivity to missed opportunities could be significantly predicted by the degree of decrease in alpha oscillation., Conclusion: One-week attentional deployment training could modulate negative emotion in StD individuals and the degree of change in alpha oscillation might act as an objective indicator for the effectiveness of training., Significance: Our study provides a convenient and effective approach to alleviate the negative emotion of StD individuals., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Depressed individuals exhibit altered sensitivity to both positive and negative social contact, and may not reap the same psychological and emotional benefits to socializing as non-depressed individuals. Although depressive symptoms and loneliness predict social withdrawal and decreased pleasure, little is currently understood about immediate affective arousal dynamics during real-time socializing. Using a novel ambulatory protocol that tracked both objective features of affective arousal (electrodermal activity) and subjective valence (self-reported) during college students' social interactions, we evaluated the moderating role of depression and loneliness symptoms on the associations between socializing with others (specifically, with a romantic partner, a close friend, or a group of friends) and the arousal and valence dimensions of affect. Among a racially and ethnically diverse sample of 118 college students (64% African American/Black/Continental African, 20% Latinx, 8% Asian, and 8% White) recruited from a large, predominantly White Midwestern university, those lower in depression and loneliness symptomatology evinced decreased average arousal (Β = -0.10, SE = 0.04, p < .01) when in relaxed and intimate socializing contexts (e.g., with a romantic partner and a close friend), consistent with the idea that these contexts facilitate important opportunities for psychological rest and recovery. Those lower in depression and loneliness symptoms also showed higher average arousal when socializing in the energizing context of being with a group of friends. Overall, the results suggest psychopathology is reflected in patterns of sympathetic arousal when socializing, with more depressed and lonely individuals generally feeling worse while receiving fewer psychophysiological rewards in multiple socializing contexts., (© 2024 Society for Psychophysiological Research.)

World Health Organization (WHO) has identified depression as a significant contributor to global disability, creating a complex thread in both public and private health. Electroencephalogram (EEG) can accurately reveal the working condition of the human brain, and it is considered an effective tool for analyzing depression. However, manual depression detection using EEG signals is time-consuming and tedious. To address this, fully automatic depression identification models have been designed using EEG signals to assist clinicians. In this study, we propose a novel automated deep learning-based depression detection system using EEG signals. The required EEG signals are gathered from publicly available databases, and three sets of features are extracted from the original EEG signal. Firstly, spectrogram images are generated from the original EEG signal, and 3-dimensional Convolutional Neural Networks (3D-CNN) are employed to extract deep features. Secondly, 1D-CNN is utilized to extract deep features from the collected EEG signal. Thirdly, spectral features are extracted from the collected EEG signal. Following feature extraction, optimal weights are fused with the three sets of features. The selection of optimal features is carried out using the developed Chaotic Owl Invasive Weed Search Optimization (COIWSO) algorithm. Subsequently, the fused features undergo analysis using the Self-Attention-based Gated Densenet (SA-GDensenet) for depression detection. The parameters within the detection network are optimized with the assistance of the same COIWSO. Finally, implementation results are analyzed in comparison to existing detection models. The experimentation findings of the developed model show 96% of accuracy. Throughout the empirical result, the findings of the developed model show better performance than traditional approaches.

Depression is a highly prevalent and debilitating mental disorder that often begins in adolescence. However, it remains unclear whether adults and adolescents with depression exhibit common or distinct brain dysfunctions during reward processing. We aimed to identify common and separable neurofunctional alterations during receipt of rewards and brain structure in adolescents and adults with depression. A coordinate-based meta-analysis was employed using Seed-based d mapping with permutation of subject images (SDM-PSI). Compared with healthy controls, both age groups exhibited common activity decreases in the right striatum (putamen, caudate) and subgenual ACC. Adults with depression showed decreased reactivity in the right putamen and subgenual ACC, while adolescents with depression showed decreased activity in the left mid cingulate, right caudate but increased reactivity in the right postcentral gyrus. This meta-analysis revealed shared (caudate) and separable (putamen and mid cingulate cortex) reward-related alterations in adults and adolescents with depression. The findings suggest age-specific neurofunctional alterations and stress the importance of adolescent-specific interventions that target social functions., Competing Interests: Declaration of Competing Interest None reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Negative attentional biases and self-schemas have been implicated in the development of depression. Research has indicated that a larger late positive potential (LPP) to negative self-referential words is associated with depression-as well as a maternal history of depression, an indicator of risk. However, it is unclear whether the LPP to self-referential words predicts the actual development of depression. In the current study, we examined whether electrocortical reactivity during self-referential processing predicted the development of depression across adolescence., Methods: The sample consisted of 165 8- to 14-year-old girls with no lifetime history of a depressive disorder who completed the self-referential encoding task while electroencephalography was recorded at a baseline assessment. Participants and their parent completed the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children at the baseline and 2-, 4-, and 6-year follow-up assessments., Results: Results indicated that a larger LPP to negative self-referential words at baseline predicted an increased likelihood of developing chronic-intermittent depression (i.e., persistent and/or recurrent), but not nonchronic, single-episode depression, across adolescence. In contrast, neither self-referential encoding task recall biases nor the LPP to positive self-referential words predicted the development of either type of depression., Conclusions: The results of the current study suggest that electrocortical reactivity associated with a negative self-schema in late childhood predicts the development of a more pernicious subtype of depression across adolescence. Moreover, the current study highlights the importance of considering clinical course in the examination of biomarkers of risk for depression., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Depression is a prevalent mental disorder that affects a significant portion of the global population. Despite recent advancements in EEG-based depression recognition models rooted in machine learning and deep learning approaches, many lack comprehensive consideration of depression's pathogenesis, leading to limited neuroscientific interpretability. To address these issues, we propose a hemisphere asymmetry network (HEMAsNet) inspired by the brain for depression recognition from EEG signals. HEMAsNet employs a combination of multi-scale Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) blocks to extract temporal features from both hemispheres of the brain. Moreover, the model introduces a unique 'Callosum-like' block, inspired by the corpus callosum's pivotal role in facilitating inter-hemispheric information transfer within the brain. This block enhances information exchange between hemispheres, potentially improving depression recognition accuracy. To validate the performance of HEMAsNet, we first confirmed the asymmetric features of frontal lobe EEG in the MODMA dataset. Subsequently, our method achieved a depression recognition accuracy of 0.8067, indicating its effectiveness in increasing classification performance. Furthermore, we conducted a comprehensive investigation from spatial and frequency perspectives, demonstrating HEMAsNet's innovation in explaining model decisions. The advantages of HEMAsNet lie in its ability to achieve more accurate and interpretable recognition of depression through the simulation of physiological processes, integration of spatial information, and incorporation of the Callosum-like block.

As depressive symptom is considered a prodrome, a risk factor for progression from mild cognitive impairment (MCI) to dementia, improving depressive symptoms should be considered a clinical priority in patients with MCI undergoing transcranial direct current stimulation (tDCS) intervention. We aimed to comprehensively evaluate the efficacy of the home-based and remotely monitored tDCS in patients with both MCI and depression, by integrating cognitive, psychological, and electrophysiological indicators. In a 6-week, randomized, double blind, and sham-controlled study, 37 community-dwelling patients were randomly assigned to either an active or a sham stimulation group, and received 30 home-based sessions of 2 mA tDCS for 30 min with the anode located over the left and cathode over the right dorsolateral prefrontal cortex. We measured depressive symptoms, neurocognitive function, and resting-state electroencephalography. In terms of effects of both depressive symptoms and cognitive functions, active tDCS was not significantly different from sham tDCS. However, compared to sham stimulation, active tDCS decreased and increased the activation of delta and beta frequencies, respectively. Moreover, the increase in beta activity was correlated with the cognitive enhancement only in the active group. It was not possible to reach a definitive conclusion regarding the efficacy of tDCS on depression and cognition in patients with both MCI and depression. Nevertheless, the relationship between the changes of electrophysiology and cognitive performance suggests potential neuroplasticity enhancement implicated in cognitive processes by tDCS., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism., Methods: Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected., Results: High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects ( r  = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions., Conclusions: Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one's vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

Background:  Cognitive dysfunction is frequently seen in multiple sclerosis (MS). However, there are conflicting findings regarding the factors it is associated with., Objective:  To investigate the relationship between aerobic capacity, strength, disability, depression, fatigue, and cognitive reserve and function., Methods:  The mobile applications Trail Making Test (TMT A-B), Digit Span Test (DST), Visuospatial Memory Test (VSMT), and Tap Fast were used in the cognitive function evaluation. Functional performance was assessed with the 6-minute walk test (6MWT), 5-Time Sit-to-Sand (5STS) test, and grip strength. Cognitive Reserve Index (CRI), Beck Depression Inventory, Fatigue Severity Scale (FSS), and Nottingham Health Profile were also used., Results:  A significant difference was found between the MS and control groups only in the 6MWT, STS-5, grip strength, TMT, VSMT, and Tap Fast. Good correlation was found between the TMT-A and 6MWT and physical mobility. A fair correlation was shown between grip strength, energy, and pain status. A good correlation was found between TMT-B and 6MWT, and a fair relationship with disability, cognitive reserve, and pain. Good correlation was observed between the DST and 6MWT, left grip strength, pain, and energy status; fair correlations were found between right grip strength, cognitive reserve, and physical mobility. Good correlation was found between the VSMT and energy. A fair relationship between disability, cognitive reserve, and pain was demonstrated. Good correlation was observed between the Tap Fast score and disability, 5STS, FSS, energy, and physical mobility. A fair relationship was found between pain and social isolation., Conclusion:  It has been shown that cognitive performance in MS is related to disability, functional performance, cognitive reserve, fatigue, and general health., Trial Registration:  NCT06084182., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Theories of adolescent development suggest that elevated neural sensitivity to social evaluation confers tradeoffs for adolescents' wellbeing, promoting adaptation to changing social contexts but increasing risk for emotional distress and depression. This study investigated whether the association between neural processing of peer feedback and depressive symptoms depends on teacher-reported executive function (EF) ability in adolescent girls. Girls showed activation to negative and positive peer feedback in regions implicated in social-emotional processing that interacted with EF to predict depressive symptoms. Specifically, activation predicted more depression in youth with poorer EF but less depression in youth with better EF, suggesting that the impact of increased social sensitivity may depend on youths' ability to regulate this sensitivity in adaptive ways., (© 2024 Wiley Periodicals LLC.)

Introduction: Depression and sleep disturbances are commonly seen non-motor symptoms in patients with Parkinson's disease (PD). This study used polysomnography to examine the relationship between mild-moderate depression in PD and sleep characteristics, particularly slow wave activities (SWA)., Methods: 59 PD patients were split into two groups: nd-PD (n = 27) (patients with PD without depression) and d-PD (n = 32) (patients with PD with mild-moderate depression). Their clinical features, polysomnography parameters, and demographics were evaluated. Early and late sleep SWA spectrum densities and overnight SWA decline in different brain regions were particularly analyzed., Results: Non-rapid eye movement 3 (N3) sleep duration and percentage were greater in the d-PD group. N3 percentage was linked to depression (p = 0.014). During late sleep, higher SWA (0.5-4Hz) in the frontal and central regions, higher low-SWA (0.5-2Hz) in the whole brain, central and occipital regions, and higher high-SWA (2-4Hz) in the frontal region was observed in the d-PD group. During early sleep, there was also higher low-SWA (0.5-2Hz) in the occipital region. Patients in d-PD group exhibited reduced overnight high-SWA (2-4Hz) decline (Δhigh-SWA) in the whole brain and occipital regions. Δhigh-SWA(2-4Hz) in the occipital region were associated with depression (p = 0.049)., Conclusion: PD patients with mild-moderate depression have impaired slow wave sleep, exhibiting as increased N3 sleep, SWA, and reduced overnight SWA decline. This implies that synaptic strength reduction during sleep and impaired synaptic homeostasis regulation may be associated with depression in PD. Reduced overnight high-SWA decline in the occipital region may serve as a novel electrophysiological biomarker for indicating depression in PD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Perceived stress is an acknowledged risk factor for subthreshold depression (StD), and fluctuations in perceived stress are thought to disrupt the harmony of brain networks essential for emotional and cognitive functioning. This study aimed to elucidate the relationship between eye-open (EO) and eye-closed (EC) states, perceived stress, and StD. We recruited 27 individuals with StD and 33 healthy controls, collecting resting state fMRI data under both EC and EO conditions. We combined intrinsic connectivity and seed-based functional connectivity analyses to construct the functional network and explore differences between EC and EO conditions. Graph theory analysis revealed weakened connectivity strength in the right superior frontal gyrus (SFG) and right median cingulate and paracingulate gyrus (MCC) among participants with StD, suggesting an important role for these regions in the stress-related emotions dysregulation. Notably, altered SFG connectivity was observed to significantly relate to perceived stress levels in StD, and the SFG connection emerges as a neural mediator potentially influencing the relationship between perceived stress and StD. These findings highlight the role of SFG and MCC in perceived stress and suggest that understanding EC and EO states in relation to these regions is important in the neurobiological framework of StD. This may offer valuable perspectives for early prevention and intervention strategies in mental health disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors have no competing interests to declare.

Research investigating whether depression is an adaptation or a disorder has been hindered by the lack of an experimental paradigm that can test causal relationships. Moreover, studies attempting to induce the syndrome often fail to capture the suite of feelings, thoughts, and behaviors that characterize depression. An experimental paradigm for triggering depressive symptoms can improve our etiological understanding of the syndrome. The present study attempts to induce core symptoms of depression, particularly those related to rumination, in a healthy, nonclinical sample through a controlled social experiment. These symptoms are sad or depressed mood, anhedonia, feelings of worthlessness or guilt, and difficulty concentrating. One hundred and thirty-four undergraduate students were randomly assigned to either an exclusion (E) or control (C) group. Participants in the exclusion group were exposed to a modified Cyberball paradigm, designed to make them feel socially excluded, followed by a dual-interference task to assess whether their exclusion interfered with their working memory. Excluded participants: (a) self-reported a significant increase in sadness and decrease in happiness, but not anxiety or calmness; (b) scored significantly higher in four of five variables related to depressive rumination; and (c) performed significantly worse on a dual-interference task, suggesting an impaired ability to concentrate. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Depression is a global mental disorder, and traditional diagnostic methods mainly rely on scales and subjective evaluations by doctors, which cannot effectively identify symptoms and even carry the risk of misdiagnosis. Brain-Computer Interfaces inspired deep learning-assisted diagnosis based on physiological signals holds promise for improving traditional methods lacking physiological basis and leads next generation neuro-technologies. However, traditional deep learning methods rely on immense computational power and mostly involve end-to-end network learning. These learning methods also lack physiological interpretability, limiting their clinical application in assisted diagnosis., Methodology: A brain-like learning model for diagnosing depression using electroencephalogram (EEG) is proposed. The study collects EEG data using 128-channel electrodes, producing a 128×128 brain adjacency matrix. Given the assumption of undirected connectivity, the upper half of the 128×128 matrix is chosen in order to minimise the input parameter size, producing 8,128-dimensional data. After eliminating 28 components derived from irrelevant or reference electrodes, a 90×90 matrix is produced, which can be used as an input for a single-channel brain-computer interface image., Result: At the functional level, a spiking neural network is constructed to classify individuals with depression and healthy individuals, achieving an accuracy exceeding 97.5 %., Comparison With Existing Methods: Compared to deep convolutional methods, the spiking method reduces energy consumption., Conclusion: At the structural level, complex networks are utilized to establish spatial topology of brain connections and analyse their graph features, identifying potential abnormal brain functional connections in individuals with depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Monozygotic twins share the same genotype; however, they can be phenotypically discordant on various traits. Studying discordant monozygotic twins allows the investigation of differences in associations between symptoms and psychopathological risk factors, controlled for shared genetic liability. The network approach to psychopathology suggests that depressive symptoms, along with risk and protective factors (e.g., cognition, daily activities), form a complex system of mutually interacting components. We compared monozygotic twins discordant for lifetime depression on their respective extended networks of depressive symptoms, cognitive functions and daily activities (intellectual, physical, social), and evaluated if these networks differ in their associations between variables and in the role of each variable within the network. Regularized partial correlations investigated the networks' composition in 147 monozygotic twin pairs discordant for depression from the Danish Twin Registry. Affected twins had stronger overall associations within their network of depressive symptoms, cognitive functions and daily activities than their unaffected co-twins, while the importance of the network components' associations did not differ between the co-twins. In affected twins, decreased frequency in experiencing happiness had the strongest association with remaining variables (i.e., the most influence in activating other network elements). Also, variables from different groups were significantly associated (e.g., loneliness with delayed memory, pessimism with low social activities, verbal learning with intellectual activities). In unaffected twins, both mood symptoms and cognitive functions were important, but between-groups associations were quasi-absent. These results suggest that external events affecting the ability to feel happiness likely trigger the psychopathological process (depression network activation), independently from the genetic predisposition to depression., Competing Interests: Declaration of competing interest The authors declare none., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Electroconvulsive shocks (ECS) and ketamine are antidepressant treatments with a relatively fast onset of therapeutic effects compared to conventional medication and psychotherapy. While the exact neurobiological mechanisms underlying the antidepressant response of ECS and ketamine are unknown, both interventions are associated with neuroplasticity. Restoration of neuroplasticity may be a shared mechanism underlying the antidepressant efficacy of these interventions. In this systematic review, literature of animal models of depression is summarized to examine the possible role of neuroplasticity in ECS and ketamine on a molecular, neuronal, synaptic and functional level, and specifically to what extent these mechanisms are shared between both interventions. The results highlight that hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) levels are consistently increased after ECS and ketamine. Moreover, both interventions positively affect glutamatergic neurotransmission, astrocyte and neuronal morphology, synaptic density, vasculature and functional plasticity. However, a small number of studies investigated these processes after ECS. Understanding the shared fundamental mechanisms of fast-acting antidepressants can contribute to the development of novel therapeutic approaches for patients with severe depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Witnessing emotional expressions in others triggers physiological arousal in humans. The current study focused on pupil responses to emotional expressions in a community sample as a physiological index of arousal and attention. We explored the associations between parents' and offspring's responses to dynamic facial expressions of emotion, as well as the links between pupil responses and anxiety/depression. Children (N = 90, M Age  = 10.13, range = 7.21-12.94, 47 girls) participated in this lab study with one of their parents (47 mothers). Pupil responses were assessed in a computer task with dynamic happy, angry, fearful, and sad expressions, while participants verbally labeled the emotion displayed on the screen as quickly as possible. Parents and children reported anxiety and depression symptoms in questionnaires. Both parents and children showed stronger pupillary responses to negative versus positive expressions, and children's responses were overall stronger than those of parents. We also found links between the pupil responses of parents and children to negative, especially to angry faces. Child pupil responses were related to their own and their parents' anxiety levels and to their parents' (but not their own) depression. We conclude that child pupils are sensitive to individual differences in parents' pupils and emotional dispositions in community samples., (© 2024 The Author(s). Developmental Psychobiology published by Wiley Periodicals LLC.)

Maternal depression is a risk factor for future mental health problems in offspring, with stress-system function as a candidate vulnerability factor. Here we present initial validation of an online matching-task (MT) paradigm in young children exposed to maternal depression (N = 40), a first in stressor-paradigm research for this age group. Investigations of stress-system reactivity that can be conducted online are an innovative assessment approach, accelerated by the COVID-19 pandemic. Results indicate high feasibility, with a >75% data collection success rate across measures, similar-to or better-than in-person success rates in young children. Overall, the online MT elicited significant heart rate but not cortisol reactivity. Individual differences in child mental health symptoms were a moderator of reactivity to the stressor such that children with lower, but not higher, behavioral problems exhibited the typical pattern of cortisol reactivity to the online MT. Results are aligned with allostatic load models, which suggest downregulation of stress-system reactivity as a result of experiencing adversity and mental health vulnerability. Consistent with in-person research, this suggests that an early phenotype for the emergence of behavior problems may be linked to altered stress-system reactivity. Results hold potential clinical implications for intervention development and the future of online stress-system research. Trial Registration: Clinical Trial Registration: NCT04639557; (Building Regulation in Dual Generations-Telehealth Model [BRIDGE])., (© 2024 The Author(s). Developmental Psychobiology published by Wiley Periodicals LLC.)

People with human immunodeficiency virus (HIV) (PWH) are at an increased risk for impaired everyday functioning and they may also experience poor awareness of their functional status. This study identified factors associated with (1) subjective and objective instrumental activities of daily living (IADLs) and (2) awareness of functional capacity in PWH. In this cross-sectional study, 236 PWH completed a neurobehavioral assessment, including self-report and performance-based measures of IADLs. Multiple regressions were performed to identify demographic, personality, and cognitive factors contributing to subjective and objective evaluation of everyday functioning, as well as discrepancy between self-report and performance-based measures of IADLs. Results indicated that increased depression was associated with worsened self-report of everyday functioning but not performance of IADLs. Cognitive function and age were associated with IADL performance. Most participants (58.1%) demonstrated a discrepancy between self-report and actual performance of IADLs. Worse processing speed was correlated with greater discrepancy. Inaccurate self-reporters had worse overall cognitive functioning and lower levels of personality traits, including openness, conscientiousness, and agreeableness. In conclusion, self-report and actual performance of IADLs in PWH is influenced by different factors. Self-report may be more affected by psychological variables, such as mood and personality, while actual performance is more sensitive to age and cognitive function.

Purpose: Identify the presence of a dysfunctional electroencephalographic (EEG) pattern in individuals with sickle cell disease (SCD) and hip osteonecrosis, and assess its potential associations with depression, anxiety, pain severity, and serum levels of brain-derived neurotrophic factor (BDNF)., Methods: In this cross-sectional investigation, 24 SCD patients with hip osteonecrosis and chronic pain were matched by age and sex with 19 healthy controls. Resting-state EEG data were recorded using 32 electrodes for both groups. Power spectral density (PSD) and peak alpha frequency (PAF) were computed for each electrode across Delta, Theta, Alpha, and Beta frequency bands. Current Source Density (CSD) measures were performed utilizing the built-in Statistical nonparametric Mapping Method of the LORETA-KEY software., Results: Our findings demonstrated that SCD individuals exhibited higher PSD in delta and theta frequency bands when compared to healthy controls. Moreover, SCD individuals displayed increased CSD in delta and theta frequencies, coupled with decreased CSD in the alpha frequency within brain regions linked to pain processing, motor function, emotion, and attention. In comparison to the control group, depression symptoms, and pain intensity during hip abduction were positively correlated with PSD and CSD in the delta frequency within the parietal region. Depression symptoms also exhibited a positive association with PSD and CSD in the theta frequency within the same region, while serum BDNF levels showed a negative correlation with CSD in the alpha frequency within the left insula., Conclusion: This study indicates that individuals with SCD experiencing hip osteonecrosis and chronic pain manifest a dysfunctional EEG pattern characterized by the persistence of low-frequency PSD during a resting state. This dysfunctional EEG pattern may be linked to clinical and biochemical outcomes, including depression symptoms, pain severity during movement, and serum BDNF levels., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This paper provides a summary of the role of nitric oxide (NO) and hormones in the development of chronic stress, anxiety, depression, and post-traumatic stress disorder (PTSD). These mental health conditions are prevalent globally and involve complex molecular interactions. Although there is a significant amount of research and therapeutic options available, the underlying mechanisms of these disorders are still not fully understood. The primary pathophysiologic processes involved in chronic stress, anxiety, depression, and PTSD include dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the intracellular influence of neuronal nitric oxide synthase (nNOS) on transcription factors, an inflammatory response with the formation of nitrergic oxidative species, and reduced serotonergic transmission in the dorsal raphe nucleus. Despite the extensive literature on this topic, there is a great need for further research to clarify the complexities inherent in these pathways, with the primary aim of improving psychiatric care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse-compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson's disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson's disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson's disease and 167 age- and sex-matched healthy participants from Parkinson's Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse-compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse-compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson's disease and psychosocial causes., (© 2024. The Author(s).)

Emotion studies have commonly reported impaired emotional processing in individuals with heightened anhedonic depressive symptoms, as typically measured by collecting single subjective ratings for a given emotional cue. However, the interindividual variation in moment-to-moment emotional reactivity, and associated time-varying brain networks recruitment as emotions are unfolding, remains unclear. In this study, we filled this gap by using the unique temporal characteristics of music to investigate behavioural and brain network dynamics as a function of anhedonic depressive symptoms severity. Thirty-one neurotypical participants aged 18-30 years completed anhedonic depression questionnaires and then continuously rated happy, neutral and sad pieces of music whilst undergoing MRI scanning. Using a unique combination of dynamic approaches to behavioural (i.e., emotion dynamics) and fMRI (i.e., leading eigenvector dynamics analysis; LEiDA) data analysis, we found that participants higher in anhedonic depressive symptoms exhibited increased recruitment of attentional networks and blunted emotional response to both happy and sad musical excerpts. Anhedonic depression mediated the relationship between attentional networks recruitment and emotional blunting, and the elevated recruitment of attentional networks during emotional pieces of music carried over into subsequent neutral music. Future studies are needed to investigate whether these findings could be generalised to a clinical population (i.e., major depressive disorder)., (© 2024. The Author(s).)

Introduction: Depression can exacerbate diabetes by impairing self-care behaviors and increasing the risk of complication; however, the underlying mechanism is still unclear. Given the suggested associations between walking activity, depression status, and blood glucose levels this study explores the intricate relationship between depression and blood glucose (BG) control, with a focus on walking activity as a behavioral mediator. The purpose of this study is to examine walking activity's mediating role in depression's impact on BG levels, investigating and validating the non-linear association between BG levels and walking activity. This retrospective real-world study demonstrates the potential of regular walking activity as a simple and accessible intervention to mitigate the negative effects of depression on BG levels in T2D and prediabetes., Methods: A cohort of 989 users with T2D and prediabetes, who regularly tracked their steps levels and BG levels for 12 months using the Dario digital health platform was evaluated. The mediating role of the monthly average number of steps on the relationship between the self-reported depression status and lagged monthly average BG was assessed. Additionally, the association between monthly walking activity and monthly average BG was tested using a piecewise linear mixed effects model., Results: Users with self-reported depression demonstrated increased BG levels compared to users without depression (B=8.00, P=.01). The association between depression and monthly average number of steps was significant (B=-.27, P<.005) and monthly average number of steps significantly predicted the following months' average BG (B=-.81, P=.001), adjusting for depression. The monthly average number of steps significantly mediated the effect of self-reported depression on the following month's average BG (M=.22, P<.005). Further sensitivity analysis demonstrated model robustness over various periods. Finally, non-linear dynamics of walking activity over time was validated using unseen data showing a decrease in monthly average BG for users with over an average of 400 steps per day (B=-1.87, P<.01)., Discussion: This study shows how regular walking may reduce the negative impact of depression on BG levels in people with T2D. Our findings advocate for the integration of walking activity into treatment protocols as a cost-effective, accessible intervention strategy to improve glycemic management and depressive symptoms in this population., Competing Interests: YF-H, IB, and OM are employees at Dario Health. MR and DH serve as Dario Health scientific advisory board members. PG has received a consulting fee to assist with analyses but otherwise has no conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fundoiano-Hershcovitz, Breuer Asher, Kantor, Rahmon, Ritholz, Horwitz, Manejwala and Goldstein.)

Individuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes., (© 2024. The Author(s).)

Stress, which triggers numerous physiological and behavioral responses in the organism, is a significant risk factor that contributes to the development of psychiatric disorders such as depression and anxiety. This study aimed to investigate the inflammation, oxidative stress status, anxiety, and depression-like behaviors of adolescent rodents exposed to chronic intermittent cold stress. Adolescent male rats were subjected to a modified chronic intermittent cold stress model (21 days, 1 hour/day, 4 °C). Depression-like behaviors were evaluated using the sucrose preference and forced swimming tests, while anxiety-like behaviors were assessed using the open field, elevated plus maze, and light-dark box tests. We measured levels of cortisol, tumor necrosis factor-α, interleukin-1β, brain-derived natriuretic factor, reactive oxygen species, malondialdehyde, total oxidants and antioxidants, and other chemicals in the prefrontal cortex, thalamus, striatum, and hippocampus brain regions of rats using ELISA and colorimetric methods. Data were analyzed using Student's t-test and Pearson correlation analysis. After the cold stress treatment, both anxiety and depression-like behaviors increased remarkably in the subjects. Our study revealed significant changes in various brain regions among the stress-exposed subjects. Cold stress resulted in decreased BDNF levels in the prefrontal cortex and striatum (p < 0.05), increased cortisol levels in the prefrontal cortex (p < 0.05), increased IL-1β levels in the hippocampus and thalamus (p < 0.05), increased protein carbonyl levels in the striatum (p < 0.05), and decreased TAS in the prefrontal cortex and thalamus (p < 0.05). Adolescent rats exposed to cold exhibit both anxiety- and depression-like behaviors. This study observed an increase in inflammation in various brain regions, yet the responses to stress varied. Our findings suggest that adolescence is a period of heightened sensitivity to stress, which can lead to dramatic consequences., Competing Interests: Declaration of Competing Interest The authors declare they have no actual or potential competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Humans can decode emotional states from the body odors of the conspecifics and this type of emotional communication is particularly relevant in conditions in which social interactions are impaired, as in depression and social anxiety. The present study aimed to explore how body odors collected in happiness and fearful conditions modulate the subjective ratings, the psychophysiological response and the neural processing of neutral faces in individuals with depressive symptoms, social anxiety symptoms, and healthy controls (N = 22 per group). To this aim, electrocardiogram (ECG) and HD-EEG were recorded continuously. Heart Rate Variability (HRV) was extracted from the ECG as a measure of vagal tone, event-related potentials (ERPs) and event-related spectral perturbations (ERPSs) were extracted from the EEG. The results revealed that the HRV increased during the fear and happiness body odors conditions compared to clean air, but no group differences emerged. For ERPs data, repeated measure ANOVA did not show any significant effects. However, the ERPSs analyses revealed a late increase in delta power and a reduced beta power both at an early and a late stage of stimulus processing in response to the neutral faces presented with the emotional body odors, regardless of the presence of depressive or social anxiety symptoms. The current research offers new insights, demonstrating that emotional chemosignals serve as potent environmental cues. This represents a substantial advancement in comprehending the impact of emotional chemosignals in both individuals with and without affective disorders., (© 2024. The Author(s).)

Introduction: No studies systematically examined sex differences in neural mechanisms underlying depression and mania/hypomania risk., Method: 80 females and 35 males, n = 115(age21.6±1.90) were scanned using 3TfMRI during an implicit emotional-faces task. We examined neural activation to all emotional faces versus baseline, using an anatomical region-of-interest mask comprising regions supporting emotion and salience processing. Sex was a covariate. Extracted parameter estimates(FWE < 0.05,k > 15), age, IQ and their sex interactions were independent variables(IV) in two penalized regression models: dependent variable either MOODS-SR-lifetime, depressive or manic domain score as measures of mania and depression risk. Subsequent Poisson regression models included the non-zero variables identified in the penalized regression models. We tested each model in 2 independent samples. Test sample-I,n = 108(21.6 ± 2.09 years,males/females = 33/75); Test sample-II,n = 93(23.7 ± 2.9 years,males/females = 31/62)., Results: Poisson regression models yielded significant relationships with depression and mania risk: Positive correlations were found between right fusiform activity and depression(beta = 0.610) and mania(beta = 0.690) risk. There was a significant interaction between sex and right fusiform activity(beta = -0.609) related to depression risk, where females had a positive relationship than; and a significant interaction(beta = 0.743) between sex and left precuneus activity related to mania risk, with a more negative relationship in females than males. All findings were replicated in the test samples(qs < 0.05,FDR)., Limitations: No longitudinal follow-up., Conclusion: Greater visual attention to emotional faces might underlie greater depression and mania risk, and confer greater vulnerability to depression in females, because of heightened visual attention to emotional faces. Females have a more negative relationship between mania risk and left precuneus activity, suggesting heightened empathy might be associated with reduced mania/hypomania risk in females more than males., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample., Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging., Results: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05)., Limitations: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression)., Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity., Competing Interests: Declaration of competing interest Dr. Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. Dr. Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or conflicts of interest. All authors have approved the final article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bulimia nervosa (BN) is a condition marked by a typical cyclical behavioural activity, characterized by restrictions, binges and vomiting, as well as a disturbance of the emotional value of food. Food stimuli acquire excessive relevance, giving rise to a succession of states of excitement and anxiety. The depressive condition accompanies very often BN. Most people with BN also experience one or more anxiety disorders. The aim of the review is to identify a link at a central and peripheral level that connects an eating disorder with a mood state. Altered nervous mechanisms are involved in BN. Among the cerebral areas, the insula is functionally compromised in BN. The insula is also implicated in depressive states. The insula is the primary gustatory cortex, where gustatory sensory information such as taste discrimination and higher cognitive functions such as food anticipation and reward are processed. The insula is anatomically connected to a wide range of cortical, limbic and paralimbic structures, and functionally implicated in high-order cognition, emotional responses, and empathic processes. The insula plays a crucial role in empathy, or in the ability to share the emotional states of others, and in particular negative emotions. In fact, the insular cortex is also activated in conditions of anxiety and depression. One of the pathophysiological factors that influences bulimia and depression is the composition of gut microbiota, as there is a strong association between the microbial signature and the brain function. Gut dysbiosis condition may contribute to the development of eating disorders, including BN. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of eating disorders. From this emerges the importance of adequate probiotic integration as a preventive and/or therapeutic tool in these pathologies., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is reported to be the most common type of autosomal dominant cerebellar ataxia (ADCA). SCA3 patients suffer from a progressive decline in motor coordination and other disease-associated symptoms. Moreover, recent studies have reported that SCA3 patients also exhibit symptoms of cerebellar cognitive affective syndrome (CCAS). We previously observed signs of CCAS in mouse model of SCA3. Particularly, SCA3-84Q mice suffer from anxiety, recognition memory decline, and also exhibit signs of low mood and aversion to activity. Here we studied the effect of long-term injections of SK channels activator chlorzoxazone (CHZ) together and separately with the folic acid (FA) on the cerebellar Purkinje cell (PC) firing and histology, and also on the motor and cognitive functions as well as mood alterations in SCA3-84Q hemizygous transgenic mice. We realized that both CHZ and CHZ-FA combination had similar positive effect on pure cerebellum impairments including PC firing precision, PC histology, and motor performance in SCA3-84Q mice. However, only the CHZ-FA combination, but not CHZ, had significantly ameliorated the signs of anxiety and depression, and also noticeably improved recognition memory in SCA3-84Q mice. Our results suggest that the combination therapy for both ataxia and non-motor symptoms is required for the complex treatment of ADCA., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders., (© 2024. The Author(s).)

The relationship between mental disorders and sleep remains unclear. Two new studies show that the lateral habenula, a brain region associated with value-guided behavior, controls REM sleep and promotes emotional stability but also contributes to REM sleep disinhibition in depression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Psychiatric disorders with dysfunction of the lateral habenula (LHb) show sleep disturbance, especially a disinhibition of rapid eye movement (REM) sleep in major depression. However, the role of LHb in physiological sleep control and how LHb contributes to sleep disturbance in major depression remain elusive. Here, we found that functional manipulations of LHb glutamatergic neurons bidirectionally modulated both non-REM (NREM) sleep and REM sleep. Activity recording revealed heterogeneous activity patterns of LHb neurons across sleep/wakefulness cycles, but LHb neurons were preferentially active during REM sleep. Using an activity-dependent tagging method, we selectively labeled a population of REM sleep-active LHb neurons and demonstrated that these neurons specifically promoted REM sleep. Neural circuit studies showed that LHb neurons regulated REM sleep via projections to the ventral tegmental area but not to the rostromedial tegmental nucleus. Furthermore, we found that the increased REM sleep in a depression mouse model was associated with a potentiation of REM sleep-active LHb neurons, including an increased proportion, elevated spike firing, and altered activity mode. Importantly, inhibition of REM sleep-active LHb neurons not only attenuated the increased REM sleep but also alleviated depressive-like behaviors in a depression mouse model. Thus, our results demonstrated that REM sleep-active LHb neurons selectively promoted REM sleep, and a potentiation of these neurons contributed to depression-associated sleep disturbance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Several mental disorders emerge during childhood or adolescence and are often characterized by socioemotional difficulties, including alterations in emotion perception. Emotional facial expressions are processed in discrete functional brain modules whose connectivity patterns encode emotion categories, but the involvement of these neural circuits in psychopathology in youth is poorly understood. This study examined the associations between activation and functional connectivity patterns in emotion circuits and psychopathology during development. We used task-based fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC, N = 1221, 8-23 years) and conducted generalized psycho-physiological interaction (gPPI) analyses. Measures of psychopathology were derived from an independent component analysis of questionnaire data. The results showed positive associations between identifying fearful, sad, and angry faces and depressive symptoms, and a negative relationship between sadness recognition and positive psychosis symptoms. We found a positive main effect of depressive symptoms on BOLD activation in regions overlapping with the default mode network, while individuals reporting higher levels of norm-violating behavior exhibited emotion-specific lower functional connectivity within regions of the salience network and between modules that overlapped with the salience and default mode network. Our findings illustrate the relevance of functional connectivity patterns underlying emotion processing for behavioral problems in children and adolescents., (© 2024. The Author(s).)

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO 2 max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Both ruminative thought processes and adverse childhood experiences (ACEs) are well-established risk factors for the emergence and maintenance of depression. However, the neurobiological mechanisms underlying these associations remain poorly understood., Methods: We examined resting-state functional magnetic resonance imaging data (3 T Tim Trio MR scanner; Siemens, Erlangen) of 44 individuals diagnosed with an acute depressive episode. Specifically, we focused on investigating functional brain activity and connectivity within and between three large-scale neural networks associated with processes affected in depression: the default mode network (DMN), the salience network (SN), and the central executive network (CEN). Correlational and regression-based analyses were performed., Results: Our regions of interest analyses revealed that region-specific spontaneous neural activity in the anterior DMN was associated with self-reported trait rumination, specifically, the pregenual anterior cingulate cortex (pgACC). Furthermore, using a liberal statistical threshold, we found that spontaneous neural activity of the ventromedial prefrontal cortex and the pgACC were associated with depression symptom severity. Neither spontaneous neural activity in the SN and CEN nor functional connectivity within and across the investigated networks was associated with depression severity or rumination. Furthermore, there was no association between ACEs and brain activity and connectivity., Limitations: Lack of a formal control group or low-risk group for comparison., Conclusions: Overall, our results indicate network-specific changes in spontaneous brain activity, that are linked to both depression severity and rumination. Findings underscore the crucial role of the pgACC in depression and contribute to a dimensional and symptom-based understanding of depression-related network imbalances., Competing Interests: Declaration of competing interest Simone Grimm has served as a consultant to and received research support from Boehringer Ingelheim Pharma. Malek Bajbouj has served as a consultant to GH Research, Janssen, Bayer, and Boehringer Ingelheim., (Copyright © 2024. Published by Elsevier B.V.)

Early life events can have long-lasting effects that may impact the quality of life into adulthood. The link between childhood adversities and adult mental and physical health is well documented, however, the underlying mechanisms remain poorly understood. Executive functions are assumed to be a key factor in successfully dealing with cognitive-emotional challenges thereby contributing to stress resilience and mental health across the lifespan. Here, we examined whether cognitive control moderates the link between early life adversity and depression. Data was available from a sample of 424 participants aged 20-70 years (Clinicaltrials.gov: NCT05155397). They performed in the Stroop task and behavior as well as frontal theta power were recorded. Negative childhood experiences were assessed with the Childhood Trauma Questionnaire (CTQ), chronic stress was measured with the Trier Inventory for Chronic Stress (TICS) and depression symptoms with Beck's Depression Inventory (BDI). The CTQ predicted symptoms of chronic stress and depression. Regression models pointed to the TICS as a crucial mediator in the relationship between CTQ and BDI. However, parameters of cognitive control demonstrated a rather weak effect as moderators. These results indicate that chronic stress is an important mediator linking childhood trauma to depression but suggest only a limited role for cognitive control., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

People with epilepsy often suffer from comorbid psychiatric disorders, which negatively affects their quality of life. Emotion regulation is an important cognitive process that is impaired in individuals with psychiatric disorders, such as depression. Adults with epilepsy also show difficulties in emotion regulation, particularly during later-stage, higher-order cognitive processing. Yet, the spatiotemporal and frequency correlates of these functional brain deficits in epilepsy remain unknown, as do the nature of these deficits in adolescent epilepsy. Here, we aim to elucidate the spatiotemporal profile of emotional conflict processing in adolescents with epilepsy, relative to controls, using magnetoencephalography (MEG) and relate these findings to anxiety and depression symptom severity assessed with self-report scales. We hypothesized to see blunted brain activity during emotional conflict in adolescents with epilepsy, relative to controls, in the posterior parietal, prefrontal and cingulate cortices due to their role in explicit and implicit regulation around participant response (500-1000 ms). We analyzed MEG recordings from 53 adolescents (28 epilepsy [14focal,14generalized], 25 controls) during an emotional conflict task. We showed that while controls exhibited behavioral interference to emotional conflict, adolescents with epilepsy failed to exhibit this normative response time pattern. Adolescents with epilepsy showed blunted brain responses to emotional conflict in brain regions related to error evaluation and learning around the average response time (500-700 ms), and in regions involved in decision making during post-response monitoring (800-1000 ms). Interestingly, behavioral patterns and psychiatric symptom severity varied between epilepsy subgroups, wherein those with focal epilepsy showed preserved response time interference. Thus, brain responses were regressed with depression and anxiety levels for each epilepsy subgroup separately. Analyses revealed that under activation in error evaluation regions (500-600 ms) predicted anxiety and depression in focal epilepsy, while regions related to learning (600-700 ms) predicted anxiety in generalized epilepsy, suggesting differential mechanisms of dysfunction in these subgroups. Despite similar rates of anxiety and depression across the groups, adolescents with epilepsy still exhibited deficits in emotional conflict processing in brain and behavioral responses. This suggests that these deficits may exist independently from psychopathology and may stem from underlying dysfunctions that predispose these individuals to develop both disorders. Findings such as these may provide potential targets for future research and therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The different clinical presentations of fibromyalgia syndrome (FMS) might play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in patients with FMS. Understanding how these clinical presentations are associated with the clinical and neurophysiological aspects of FMS is important for the development of effective treatments., Aim: To explore the relationship of memory complaints and depressive symptoms with the different clinical and neurophysiological characteristics of FMS., Methods: Cross-sectional data analysis from a randomized clinical trial. Baseline demographics and data on physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) from 63 subjects with FMS were used. Multiple linear and logistic association models were constructed., Results: Final regression models including different sets of predictions were statistically significant (P < .001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poorer sleep quality, lower motor threshold, and higher relative theta power in the central area and were more likely to have clinical depression. Higher anxiety, pain, and theta power were associated with a higher likelihood of memory complaints., Conclusion: Depression symptoms seem to be associated with transcranial magnetic stimulation-indexed motor threshold and psychosocial variables, whereas memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms might be catalyzed or triggered by some behavioral and clinical features, such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests that the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment of FMS., Trial Registration: ClinicalTrials.gov ID NCT03371225., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The functional alterations of the brain in bipolar II depression (BDII-D) and their clinical and inflammatory associations are understudied. We aim to investigate the functional brain alterations in BDII-D and their relationships with inflammation, childhood adversity, and psychiatric symptoms, and to examine the moderating effects among these factors. Using z-normalized amplitude of low-frequency fluctuation (zALFF), we assessed the whole-brain resting-state functional activity between 147 BDII-D individuals and 150 healthy controls (HCs). Differential ALFF regions were selected as seeds for functional connectivity analysis to observe brain connectivity alterations resulting from abnormal regional activity. Four inflammatory cytokines including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) and five clinical scales including Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), and Childhood Trauma Questionnaire (CTQ) were tested and assessed in BDII-D. Partial correlations with multiple comparison corrections identified relationships between brain function and inflammation, childhood adversity, and psychiatric symptoms. Moderation analysis was conducted based on correlation results and previous findings. Compared to HCs, BDII-D individuals displayed significantly lower zALFF in the superior and middle frontal gyri (SFG and MFG) and insula, but higher zALFF in the occipital-temporal area. Only the MFG and insula-related connectivity exhibited significant differences between groups. Within BDII-D, lower right insula zALFF value correlated with higher IL-6, CRP, and emotional adversity scores, while lower right MFG zALFF was related to higher CRP and physical abuse scores. Higher right MFG-mid-anterior cingulate cortex (mACC) connectivity was associated with higher IL-1β. Moreover, IL-1β moderated associations between higher right MFG-mACC/insula connectivity and greater depressive symptoms. This study reveals that abnormal functional alterations in the right MFG and right insula were associated with elevated inflammation, childhood adversity, and depressive symptoms in BDII-D. IL-1β may moderate the relationship between MFG-related connectivity and depressive symptoms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MW is a member of the advisory boards and gave presentations for the following companies: Boehringer Ingelheim, Germany; Bayer AG, Germany; and Biologische Heilmittel Heel GmbH, Germany. MW has further conducted studies with institutional research support from HEEL and from Janssen Pharmaceutical Research for a clinical trial (IIT) on ketamine in individuals with major depression unrelated to this investigation. MW has not received any financial compensation from the above-mentioned companies. All other authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)